Nitrosation of 1-Phenyl-3-(pyridylmethyl)ureas and the Reactivity of Two Nitrosated Isomers

Abstract

1-Phenyl-3-(pyridylmethyl)ureas (I) were nitrosated with sodium nitrite under acidic conditions to give two positional isomers, 1-nitroso-1-phenyl-3-(pyridylmethyl)urea (II) and 3-nitroso-1-phenyl-3-(pyridylmethyl)urea (III). The nitrosation was carried out using several nitrosating reagents under various conditions, and each isomer was determined by means of high-performance liquid chromatography. The regioselectivity depended on the medium and reagents used. With gaseous nitrosating reagents in organic solvents at 0°C, I generated mainly III. The combination of sodium nitrite and acid (1 M perchloric acid, 1 M hydrochloric acid or 99% formic acid) gave II predominantly. However, with N₂O₃, the predominant product was dependent on the pH of the medium. The differences of chemical and antitumor activity of the nitroso isomers were also examined.